The association of matrix Gla protein isomers with calcification in capsules surrounding silicone breast implants.
The association of matrix Gla protein isomers with calcification in capsules surrounding silicone breast implants.
复制标题
基质 Gla 蛋白异构体与硅胶乳房植入物周围胶囊钙化的关联。
DOI：
10.1016/j.biomaterials.2011.07.073
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发表时间：
2011
期刊：
影响因子：
14
通讯作者：
Miller,VirginiaM
中科院分区：
文献类型：
--
作者：
Hunter,LarryW;Lieske,JohnC;Tran,NhoV;Miller,VirginiaM
植入的硅胶医用假体在邻近组织中诱导动态的组织学事件序列，导致假体周围囊形成纤维化。在某些情况下，发生包膜钙化，需要手术干预。在这项研究中，我们研究了硅凝胶填充乳房假体的包膜，以检验这种钙化可能受小维生素K依赖性蛋白、基质Gla蛋白（MGP）（一种有效的动脉钙化抑制剂）或胎球蛋白A（一种肝细胞衍生的糖蛋白，也是病理性钙化的调节剂）调节的假设。使用构象特异性抗体对外植囊组织进行免疫定位研究，发现未钙化囊细胞内存在矿化保护性γ-羧基化MGP异构体（cMGP），而无功能的羧基化不足异构体（uMGP）通常不存在。两者均在钙化囊中上调，并与矿物质斑块和邻近纤维共定位。滑膜样化生存在于一个未钙化的包膜中，其中MGP物种差异定位于假滑膜内。胎球蛋白-A定位于未钙化囊内的细胞和钙化囊内的矿物质沉积。骨诱导细胞因子骨形态发生蛋白-2定位于未钙化囊中的胶原纤维。这些结果表明，维生素K活化构象的MGP可能是维持假体周围组织健康的药理学靶点，假体周围组织包封硅胶乳房植入体以及其他植入的硅胶医疗器械。
Implanted silicone medical prostheses induce a dynamic sequence of histologic events in adjacent tissue resulting in the formation of a fibrotic peri-prosthetic capsule. In some cases, capsular calcification occurs, requiring surgical intervention. In this study we investigated capsules from silicone gel-filled breast prostheses to test the hypothesis that this calcification might be regulated by the small vitamin K-dependent protein, matrix Gla protein (MGP), a potent inhibitor of arterial calcification, or by Fetuin-A, a hepatocyte-derived glycoprotein also implicated as a regulator of pathologic calcification. Immunolocalization studies of explanted capsular tissue, using conformation-specific antibodies, identified the mineralization-protective γ-carboxylated MGP isomer (cMGP) within cells of uncalcified capsules, whereas the non-functional undercarboxylated isomer (uMGP) was typically absent. Both were upregulated in calcific capsules and co-localized with mineral plaque and adjacent fibers. Synovial-like metaplasia was present in one uncalcified capsule in which MGP species were differentially localized within the pseudosynovium. Fetuin-A was localized to cells within uncalcified capsules and to mineral deposits within calcific capsules. The osteoinductive cytokine bone morphogenic protein-2 localized to collagen fibers in uncalcified capsules. These findings demonstrate that MGP, in its vitamin K-activated conformer, may represent a pharmacological target to sustain the health of the peri-prosthetic tissue which encapsulates silicone breast implants as well as other implanted silicone medical devices.